Congenital absence of the inferior rectus muscle--diagnosis and management.

BACKGROUND: Congenital absence of the inferior rectus muscle is a rare cause of apparent inferior rectus palsy especially in the absence of associated cranial facial anomalies. METHODS: We report three cases of isolated congenital absence of the inferior rectus muscle and its successful surgical management. RESULTS: Failure of the normal embryologic development of the mesodermal complex around the eye can lead to agenesis of the extraocular muscles. In apparent palsies of the inferior rectus muscle and no definite cause, a high index of suspicion and orbital imaging can confirm the diagnosis of congenitally absent inferior rectus preoperatively. Surgical correction may involve inferior transposition of the horizontal rectus muscles. CONCLUSIONS: Although rare, congenital absence of the inferior rectus muscle is a possible cause of apparent inferior rectus muscle palsy particularly in the absence of another identifiable cause. Strabismus surgery in conjunction with intramuscular botulinum toxin injection can offer significant improvement in function and cosmesis of these patients.     

HLA-DR expression in macaque neuroendothelial cells in vitro and during SIV encephalitis

HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system.     

Development of immunofiltration assay by light addressable potentiometric sensor with genetically biotinylated recombinant antibody for rapid identification of Venezuelan equine encephalitis virus

A genetically biotinylated single chain fragment variable antibody (scFv) against Venezuelan equine encephalitis virus (VEE) was applied in a system consisting of an immunofiltration enzyme assay (IFA) with a light addressable potentiometric sensor (LAPS) for the rapid identification of VEE. The IFA involved formation of an immunocomplex sandwich consisting of VEE, biotinylated antibody, fluoresceinated antibody and streptavidin, capture of the sandwich by filtration on biotinylated membrane, and labeling of the sandwich by anti-fluorescein urease conjugate. The concentration ratio of biotinylated to fluoresceinated antibodies was investigated and optimized. By the IFA/LAPS assay, the limit of detection (LOD) of VEE was approximately 30 ng/ml, similar to that achieved when chemically biotinylated monoclonal antibody (mAb) was applied. Total assay variance of the IFA/LAPS assay for both intra- and inter-assay precision was less than 20%. Assay accuracy was measured by comparing VEE concentrations estimated by IFA/LAPS standard curve to those obtained by conventional protein assay. VEE concentrations were found to differ by no more than 10%. The IFA/LAPS assay sensitivity was approximately equal to that of a conventional enzyme-linked immunosorbent assay (ELISA) utilizing polystyrene plates and a chromogenic substrate; however, less time and effort were required for performance of the IFA/LAPS assay. More importantly, use of genetically biotinylated scFv in the IFA/LAPS assay obviates the need for chemical biotinylation of antibody with resultant possible impairment of the antigen-binding site. Furthermore, the potential for batch-to-batch variability resulting from inequality in the number of biotin molecules labeled per antibody molecule is eliminated.     

The Complement-Fixation Test in Hepatic Coccidiosis of Rabbits

Antibodies to Eimeria stiedae were measured in rabbit serum by complement fixation. The titre rose to a maximum at about the 22nd day after infection, remained at this level for about 20 days and then declined. Antibodies were still detectable up to 160 days after infection.

Evidence of past or present slight E. stiedae infection was found in clinically normal rabbits whose sera fixed complement with E. stiedae antigens.

Challenge of rabbits which had recovered from a near-fatal infection had no effect upon the complement fixation titres of their sera.

The serum of a rabbit which had been injected with alum-precipitated antigen fixed complement with E. stiedae antigens. However, the animal was still susceptible to a superimposed oral infection which had the effect of further increasing the serum titre.

     

Holt-Oram syndrome associated with the hypoplastic left heart syndrome

We present the first case of Holt-Oram syndrome associated with the lethal congenital heart defect of hypoplastic left heart syndrome. The possible pathophysiological link is explored and the need for careful genetic and cardiologic evaluation in these patients is reiterated.     

Anti-idiotypic antibodies specific for HLA in heart and kidney allograft recipients

Chronic rejection is the major threat to both heart and renal allograft survival. We have explored the possibility that some patients with anti-donor HLA antibodies (Ab1) develop specific anti-idiotypic antibodies (Ab2) which suppress the production of Ab1, and subsequently, the progression of chronic rejection. analysis of Ab2 in sera obtained from Ab1 producers showed that 22% of heart and 18% of kidney recipients produced Ab2. The 4- and 5-year actuarial graft survivals in Ab2 producers were 100% and 83%, respectively, compared to 57% in patients who formed Ab1 but not Ab2 (p<0.004). Patients carrying the DR2 alleles, DRB1*1501,*1502 or*1601 were at a lower risk of producing anti-donor HLA antibodies.     

Anti-HLA class I antibody-mediated activation of the PI3K/Akt signaling pathway and induction of Bcl-2 and Bcl-xL expression in endothelial cells

Anti-human leukocyte antigen (HLA) antibodies (Ab) have long been implicated in the process of acute and chronic allograft rejection, yet their mechanism(s) of action is not well understood. The aim of this study was to determine whether ligation of HLA class I molecules by anti-HLA Ab on the surface of human endothelial cells (EC) activates the PI3 Kinase (PI3K)/Akt signaling pathway and downstream target proteins of the cell death apparatus. We report that Ab ligation of major histocompatibility complex (MHC) class I molecules on the surface of EC triggers phosphorylation of Akt, PI3K, and recruitment of PI3K and Akt into a signaling unit with focal adhesion kinase. Signaling through class I also stimulated phosphorylation of Bad and upregulated expression of Bcl-2 and Bcl-xL. Pretreatment of EC with the PI3K inhibitor wortmannin blocked class I-mediated expression of Bcl-2, but not Bcl-xL, suggesting a role for the PI3K/Akt signaling pathway in regulation of class I-induced Bcl-2 expression. The intracellular events initiated by class I ligation were influenced by the concentration of the anti-HLA Ab with the lowest tested concentrations of Ab stimulating the highest level of Akt phosphorylation, Bcl-xL and Bcl-2 expression. Consistent with the in vitro experiments, analysis of biopsy samples from heart transplant recipients with evidence of Ab-mediated rejection exhibited increased Bcl-2 expression on the vascular endothelium. These results suggest that exposure of the graft endothelium to low concentrations of anti-HLA Ab may promote cell survival by transducing signals resulting in upregulation of cell survival genes.